For more precise control of pressure-driven flow and automation,
micropneumatic pumps integrated with the microfluidic chip have been developed
and have become popular for immunoassays. The micropneumatic pump is com-
posed of a fluid flow in a microchannel, mechanically flexible membranes such as
those made of PDMS and air chambers or valves that pneumatically deflect the
PDMS membranes by introduction of compressed air [ 44 , 67 , 68 ]. Liquid is
propelled by the peristaltic action driven by the time-phased deflection of PDMS
membranes above the fluid flow along the microchannel, and is particularly suitable
for sequential liquid delivery. Detection of host-generated antibody against infec-
tion pathogens has been demonstrated with micropnuematic pumps in microfluidic
immunoassays [ 67 ]. In this system, a capture probe was first adsorbed on the
surface of the detection zone. Serum sample, washing buffer, detection antibody
and signal generation reagents stored in separate reservoirs were sequentially
delivered to the detection zone by the micropneumatic pump. The signal generated
was then detected optically by absorbance measurement. The peristaltic action
required at least three pneumatic valves for controlled sequential deflection of the
PDMS membranes [ 69 ].
In a more recent design by Schudel et al. [ 70 ], the valve structure utilized flexible
PDMS membranes with microfabricated barrier features or gates that are lifted
away from a substrate by vacuum, thus allowing the fluid to flow. Kim et al. [ 71 ]
used these lifting gate microvalves and built pumping capabilities within
microfluidics. The pump consisted of a linear array of three microvalves in series
with cyclic actuation, and was capable of efficient and automated fluid transport.
The lifting gate structures offer enhanced and direct integration with patterned solid
substrates.
To simplify design and control algorithms, it is desirable to limit the number of
pneumatic valves required for pumping. For this, alternative designs for
micropneumatic pumps that used air chambers of different sizes interconnected
by air channels were developed [ 72 , 73 ]. Using interconnected air chambers caused
the membranes to deflect at different times, allowed for their sequential actuation
and introduced the latency required to generate peristaltic pumping action on the
PDMS membranes, but only one pneumatic valve was required. This
micropneumatic pump was used in bead-based immunoassays with flow cytometry
detection [ 44 ]. The transport of samples, washing buffer, antibody-conjugated
magnetic beads, detection antibody and sheath flow for focusing the sample stream
were all provided by the micropneumatic pump, and the entire process including
sample incubation and final detection step took 40 min.
3.3 Centrifugal Force-Driven Modalities
Centrifugal force-based microfluidic platforms have been developed and typically
built from round substrate similar to the compact disc (CD) form factor and
footprint. CD-based microfluidic systems contain networks of channels and
9 On-Chip Immunoassay for Molecular Analysis 233